Cystic fibrosis is the most common recessively inherited lethal or semilethal disease affecting primarily exocrine glands. Research outlined in this proposal is directed toward elucidating: (1) the normal and pathological pharmacological responsiveness of the eccrine sweat glands; (2) difference of the secretory products according to different pharmacologic stimuli in both normal and cystic fibrosis sweat glands; (3) intracellular events associated with secretion under various stimuli; (4) mechanisms of NaCl absorption by the sweat duct including its possible coupling with H ion transport; (5) the regulatory roles of Ca ions and various neurotransmitters on ductal reabsorptive functions; (6) the mechanism(s) of stimulus-secretion coupling at the membrane level. The methods include isolation of single eccrine sweat glands from monkeys and humans, including patients with cystic fibrosis. Sweat will be induced from the isolated cannulated eccrine sweat glands in well defined in vitro incubation conditions. The lumen of isolated segments of the sweat gland duct or secretory coil will be perfused. Likewise, electrophysiological and biochemical approaches will be made on such isolated sweat glands.